DOCSLIB.ORG

Hematopoiesis in the Bone Marrow FADD Deficiency Impairs Early

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Hematopoiesis in the Bone Marrow FADD Deficiency Impairs Early FADD Deficiency Impairs Early Hematopoiesis in the Bone Marrow Stephen Rosenberg, Haibing Zhang and Jianke Zhang This information is current as J Immunol 2011; 186:203-213; Prepublished online 29 of September 27, 2021. November 2010; doi: 10.4049/jimmunol.1000648 http://www.jimmunol.org/content/186/1/203 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2010/11/29/jimmunol.100064 Material 8.DC1 References This article cites 77 articles, 37 of which you can access for free at: http://www.jimmunol.org/content/186/1/203.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 27, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology FADD Deficiency Impairs Early Hematopoiesis in the Bone Marrow Stephen Rosenberg, Haibing Zhang, and Jianke Zhang Signal transduction mediated by Fas-associated death domain protein (FADD) represents a paradigm of coregulation of apoptosis and cellular proliferation. During apoptotic signaling induced by death receptors including Fas, FADD is required for the recruit- ment and activation of caspase 8. In addition, a death receptor-independent function of FADD is essential for embryogenesis. In previous studies, FADD deficiency in embryonic stem cells resulted in a complete lack of B cells and dramatically reduced T cell numbers, as shown by Rag12/2 blastocyst complementation assays. However, T-specific FADD-deficient mice contained normal numbers of thymocytes and slightly reduced peripheral T cell numbers, whereas B cell-specific deletion of FADD led to increased peripheral B cell numbers. It remains undetermined what impact an FADD deficiency has on hematopoietic stem cells and progenitors. The current study analyzed the effect of simultaneous deletion of FADD in multiple cell types, including bone Downloaded from marrow cells, by using the IFN-inducible Mx1-cre transgene. The resulting FADD mutant mice did not develop lymphoprolifera- tion diseases, unlike Fas-deficient mice. Instead, a time-dependent depletion of peripheral FADD-deficient lymphocytes was observed. In the bone marrow, a lack of FADD led to a dramatic decrease in the hematopoietic stem cells and progenitor- enriched population. Furthermore, FADD-deficient bone marrow cells were defective in their ability to generate lymphoid, myeloid, and erythroid cells. Thus, the results revealed a temporal requirement for FADD. Although dispensable during lym- phopoiesis post lineage commitment, FADD plays a critical role in early hematopoietic stages in the bone marrow. The Journal of http://www.jimmunol.org/ Immunology, 2011, 186: 203–213. poptosis plays a critical role in mammalian development downstream caspases and other cellular proteins, leading to cell and homeostasis (1, 2). The intrinsic apoptotic signaling death. A is mediated by the mitochondrion, involving cytochrome The importance of apoptosis in development is exemplified by C and the Bcl-2 family proteins (3). The extrinsic apoptotic the embryonic defects caused by a lack of Bcl-x or Mcl-1, members pathways are initiated by ligation of death receptors (DRs) by of the Bcl-2 family that mediate the intrinsic pathway (12, 13). either their cognate ligands or cross-linking Abs (4, 5). DRs, in- Deficiencies in proapoptotic Bcl-2 family members such as Bax cluding TNF-R1, Fas/Apo-1, and TRAIL-Rs (DR4 and DR5), and Bak resulted in interdigital webbing due to insufficient death by guest on September 27, 2021 activate a caspase cascade through the adaptor protein Fas- of superfluous cells (14, 15). Deletion of another proapoptotic Bcl- associated death domain protein (FADD), which recruits procas- 2 family member, Bim, leads to autoimmune diseases caused by pase 8 to form the death-inducing signaling complex (DISC) (6– impaired death of autoreactive lymphocytes (16). The extrinsic 11). The assembly of the DISC promotes the activation of caspase pathways are essential for maintaining homeostasis in the immune 8 by self-processing, and the resulting active caspase 8 cleaves system. In particular, a systemic loss of Fas leads to the devel- opment of an age-dependent lymphoproliferative (lpr) and auto- immune disease (17). Although expressed in a wide range of tissues, DRs do not appear Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas to play an overt role in mouse development (18–22). Interestingly, Jefferson University, Philadelphia, PA 19107 mice deficient in FADD or caspase 8 die in utero by day 9.5–10.5 Received for publication February 24, 2010. Accepted for publication October 26, 2010. of gestation (23–25). Conditional deletion of FADD or caspase 8 This work was supported in part by National Institutes of Health Grants C0A95454, following lineage commitment in double-negative thymocytes or AI083915, and AI076788, a W. W. Smith Charitable Trust grant, a Thomas Jefferson pro-B cells resulted in no significant defects in the maturation of T University Enhancement grant, and a Concern Foundation grant to J.Z. S.R. was or B cells within primary lymphoid organs (26–30). When tested supported by a National Research Service Award Training grant (T32-AI07492). in vitro, FADD2/2 or caspase 82/2 lymphocytes are defective in Address correspondence and reprint requests to Dr. Jianke Zhang, Department of 2/2 Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Univer- death receptor-induced apoptosis. Additionally, FADD and 2/2 sity, 233 South 10th Street, Room 731 BLSB, Philadelphia, PA 19107. E-mail address: caspase 8 T cells failed to expand efficiently upon stimulation [email protected] through the TCR, whereas FADD2/2 and caspase 82/2 B cells are The online version of this article contains supplemental material. impaired in TLR-induced proliferation. The effect of FADD de- Abbreviations used in this paper: BFU-E, erythroid burst-forming unit; CFU-GEMM, ficiency on the development and function of myeloid cells and granulocytic-erythrocytic-megakaryocytic-macrophagic CFU; CFU-GM, granuloma- hematopoietic progenitors has not been determined. crophagic CFU; CLP, common lymphoid progenitor; CMP, common myeloid pro- genitor; DC, dendritic cell; DISC, death-inducing signaling complex; DR, death The process of hematopoiesis commences with hematopoietic receptor; EPO, erythropoietin; ES, embryonic stem; FADD, Fas-associated death stem cells (HSCs) (31). HSCs are located in the endosteal niche domain protein; GMP, granulocytic-macrophage progenitor; HSC, hematopoietic 2 + 2 + 2 stem cell; LCCM, L-cell conditioned media; LK, Lin c-Kit Sca-1 ; lpr, lymphopro- within the bone marrow and are characterized as Lin Sca-1 c- 2 + liferative; LSK, Lin Sca-1+c-Kit+; MEP, megakaryocytic-erythroid progenitor; MPP, Kit (32). HSCs proceed to differentiate into multipotent pro- multipotent progenitor; Mut, mutant; poly(I:C), polyinosinic-polycytidylic acid; rm, genitor (MPP) cells, which subsequently develop into either recombinant mouse; SCF, stem cell factor; WT, wild-type. common lymphoid progenitors (CLPs) or common myeloid pro- Copyright Ó 2010 by The American Association of Immunologists, Inc. 0022-1767/10/$16.00 genitors (CMPs) (33, 34). The differentiation of MPPs indicates www.jimmunol.org/cgi/doi/10.4049/jimmunol.1000648 204 FADD FUNCTION IN EARLY HEMATOPOIESIS the branching point at which developing hematopoietic cells on a MoFlo cell sorter (DakoCytomation, Carpinteria, CA). To analyze commit to the lymphoid or myeloid lineage. CLPs develop into lymphocyte populations, cells were washed once with staining buffer precursors for the T, B, and NK cell populations, whereas CMPs and labeled with the following lineage-specific fluorochrome-conjugated Abs: CD4-PE, CD8-TriColor, B220-TriColor, streptavidin-R670 (Caltag- further differentiate into the granulocytic-macrophage progenitors Invitrogen), CD5-PE (eBioscience), CD3-PE, CD19-Bio, c-Kit–PE, CD25- (GMPs) and megakaryocytic-erythroid progenitors (MEPs) (33, PE, IgD-PE (BD Pharmingen), IgM-FITC (Jackson ImmunoResearch 35). GMPs differentiate into macrophages and granulocytes, Laboratories), IgM-PE, IgD-Bio (Southern Biotechnology Associates, whereas MEPs are capable of differentiation into megakaryocytes Birmingham, AL). Cells were analyzed using a Coulter Epics XL cy- tometer (Beckman Coulter, Fullerton, CA). FlowJo (Tree Star, Ashland, and erythrocytes (36, 37). Both CLPs and CMPs lead to dendritic OR) was used for the generation of histograms and dot plots. For sorting, cell (DC) differentiation; therefore, DCs can be of either myeloid bone marrow cells were resuspended in sorting medium (1:1 PBS/RPMI or lymphoid origin (34, 38, 39). 1640). GFP2 bone marrow cells were isolated using a MoFlo high-speed Apoptosis, proliferation, and differentiation of HSCs and pro- cell sorter (DakoCytomation) in the Flow Cytometry Facility at Thomas genitors are tightly
Load more

Recommended publications
  • Bone Marrow (Stem Cell) Transplant for Sickle Cell Disease Bone Marrow (Stem Cell) Transplant
    Bone Marrow (Stem Cell) Transplant for Sickle Cell Disease Bone Marrow (Stem Cell) Transplant for Sickle Cell Disease 1 Produced by St. Jude Children’s Research Hospital Departments of Hematology, Patient Education, and Biomedical Communications. Funds were provided by St. Jude Children’s Research Hospital, ALSAC, and a grant from the Plough Foundation. This document is not intended to take the place of the care and attention of your personal physician. Our goal is to promote active participation in your care and treatment by providing information and education. Questions about individual health concerns or specifi c treatment options should be discussed with your physician. For more general information on sickle cell disease, please visit our Web site at www.stjude.org/sicklecell. Copyright © 2009 St. Jude Children’s Research Hospital How did bone marrow (stem cell) transplants begin for children with sickle cell disease? Bone marrow (stem cell) transplants have been used for the treatment and cure of a variety of cancers, immune system diseases, and blood diseases for many years. Doctors in the United States and other countries have developed studies to treat children who have severe sickle cell disease with bone marrow (stem cell) transplants. How does a bone marrow (stem cell) transplant work? 2 In a person with sickle cell disease, the bone marrow produces red blood cells that contain hemoglobin S. This leads to the complications of sickle cell disease. • To prepare for a bone marrow (stem cell) transplant, strong medicines, called chemotherapy, are used to weaken or destroy the patient’s own bone marrow, stem cells, and infection fi ghting system.
    [Show full text]
  • Adaptive Immune Systems
    Immunology 101 (for the Non-Immunologist) Abhinav Deol, MD Assistant Professor of Oncology Wayne State University/ Karmanos Cancer Institute, Detroit MI Presentation originally prepared and presented by Stephen Shiao MD, PhD Department of Radiation Oncology Cedars-Sinai Medical Center Disclosures Bristol-Myers Squibb – Contracted Research What is the immune system? A network of proteins, cells, tissues and organs all coordinated for one purpose: to defend one organism from another It is an infinitely adaptable system to combat the complex and endless variety of pathogens it must address Outline Structure of the immune system Anatomy of an immune response Role of the immune system in disease: infection, cancer and autoimmunity Organs of the Immune System Major organs of the immune system 1. Bone marrow – production of immune cells 2. Thymus – education of immune cells 3. Lymph Nodes – where an immune response is produced 4. Spleen – dual role for immune responses (especially antibody production) and cell recycling Origins of the Immune System B-Cell B-Cell Self-Renewing Common Progenitor Natural Killer Lymphoid Cell Progenitor Thymic T-Cell Selection Hematopoetic T-Cell Stem Cell Progenitor Dendritic Cell Myeloid Progenitor Granulocyte/M Macrophage onocyte Progenitor The Immune Response: The Art of War “Know your enemy and know yourself and you can fight a hundred battles without disaster.” -Sun Tzu, The Art of War Immunity: Two Systems and Their Key Players Adaptive Immunity Innate Immunity Dendritic cells (DC) B cells Phagocytes (Macrophages, Neutrophils) Natural Killer (NK) Cells T cells Dendritic Cells: “Commanders-in-Chief” • Function: Serve as the gateway between the innate and adaptive immune systems.
    [Show full text]
  • Bone Marrow Biopsy
    Helpline (freephone) 0808 808 5555 [email protected] www.lymphoma-action.org.uk Bone marrow biopsy This information is about a test called a bone marrow biopsy. You might have one to check if you have lymphoma in your bone marrow. On this page What is bone marrow? What is a bone marrow biopsy? Who might need one? Having a bone marrow biopsy Is a bone marrow biopsy safe? Getting the results We have separate information about the topics in bold font. Please get in touch if you’d like to request copies or if you would like further information about any aspect of lymphoma. Phone 0808 808 5555 or email [email protected]. What is bone marrow? Bone marrow is the spongy tissue in the middle of some of the bigger bones in your body, such as your thigh bone (femur), breastbone (sternum), hip bone (pelvis) and back bones (vertebrae). Your bone marrow is where blood cells are made. It contains cells called blood (‘haemopoietic’) stem cells. Stem cells are undeveloped cells that can divide and grow into all the blood cells you need. This includes red blood cells, platelets and all the different types of white blood cells. Page 1 of 8 © Lymphoma Action Figure: The different blood cells that develop in the bone marrow What is a bone marrow biopsy? A bone marrow biopsy is a test that involves taking a sample of bone marrow to be examined under a microscope. The samples are sent to a lab where an expert examines them.
    [Show full text]
  • Terminology Resource File
    Terminology Resource File Version 2 July 2012 1 Terminology Resource File This resource file has been compiled and designed by the Northern Assistant Transfusion Practitioner group which was formed in 2008 and who later identified the need for such a file. This resource file is aimed at Assistant Transfusion Practitioners to help them understand the medical terminology and its relevance which they may encounter in the patient’s medical and nursing notes. The resource file will not include all medical complaints or illnesses but will incorporate those which will need to be considered and appreciated if a blood component was to be administered. The authors have taken great care to ensure that the information contained in this document is accurate and up to date. Authors: Jackie Cawthray Carron Fogg Julia Llewellyn Gillian McAnaney Lorna Panter Marsha Whittam Edited by: Denise Watson Document administrator: Janice Robertson ACKNOWLEDGMENTS We would like to acknowledge the following people for providing their valuable feedback on this first edition: Tony Davies Transfusion Liaison Practitioner Rose Gill Transfusion Practitioner Marie Green Transfusion Practitioner Tina Ivel Transfusion Practitioner Terry Perry Transfusion Specialist Janet Ryan Transfusion Practitioner Dr. Hazel Tinegate Consultant Haematologist Reviewed July 2012 Next review due July 2013 Version 2 July 2012 2 Contents Page no. Abbreviation list 6 Abdominal Aortic Aneurysm (AAA) 7 Acidosis 7 Activated Partial Thromboplastin Time (APTT) 7 Acquired Immune Deficiency Syndrome
    [Show full text]
  • The Bridge Between Bone Marrow Adipocytes and Hematopoietic Cells Ziru Li and Ormond A
    EDITORIALS Stem cell factor: the bridge between bone marrow adipocytes and hematopoietic cells Ziru Li and Ormond A. MacDougald Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA. E-mail: ZIRU LI - [email protected] doi:10.3324/haematol.2019.224188 hite adipocytes serve as an energy reservoir to in the bone marrow supernatant, which indicates that store excessive calories in the form of lipid BMAT is a primary source of SCF in bone marrow.5 Wdroplets and protect other tissues or organs from Deficiency of SCF in BMAT reduces the bone marrow cellu- ectopic lipid accumulation. Brown adipocytes express larity, hematopoietic stem and progenitor cells (HSPC), com- uncoupling protein 1 and are integral to adaptive thermoge- mon myeloid progenitors (CMP), megakaryocyte-erythro- nesis. Whereas the functions of adipocytes in either white or cyte progenitor (MEP) and granulocyte-monocyte progeni- brown adipose tissues are well documented, our knowledge tors (GMP) under steady-state condition. Consistent with of bone marrow adipocytes (BMA) remains in its infancy. these changes in the progenitor cells of bone marrow, mice Bone marrow adipose tissue (BMAT) occupies approximate- deficient for adipocyte SCF develop macrocytic anemia and ly 50-70% of the bone marrow volume in human adults.1 It reduction of neutrophils, monocytes and lymphocytes in cir- is a dynamic tissue and responds to multiple metabolic con- culation. In contrast to results in this study, Zhou et al. ditions. For example, BMAT
    [Show full text]
  • Nomina Histologica Veterinaria, First Edition
    NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria.
    [Show full text]
  • B-Cell Development, Activation, and Differentiation
    B-Cell Development, Activation, and Differentiation Sarah Holstein, MD, PhD Nov 13, 2014 Lymphoid tissues • Primary – Bone marrow – Thymus • Secondary – Lymph nodes – Spleen – Tonsils – Lymphoid tissue within GI and respiratory tracts Overview of B cell development • B cells are generated in the bone marrow • Takes 1-2 weeks to develop from hematopoietic stem cells to mature B cells • Sequence of expression of cell surface receptor and adhesion molecules which allows for differentiation of B cells, proliferation at various stages, and movement within the bone marrow microenvironment • Immature B cell leaves the bone marrow and undergoes further differentiation • Immune system must create a repertoire of receptors capable of recognizing a large array of antigens while at the same time eliminating self-reactive B cells Overview of B cell development • Early B cell development constitutes the steps that lead to B cell commitment and expression of surface immunoglobulin, production of mature B cells • Mature B cells leave the bone marrow and migrate to secondary lymphoid tissues • B cells then interact with exogenous antigen and/or T helper cells = antigen- dependent phase Overview of B cells Hematopoiesis • Hematopoietic stem cells (HSCs) source of all blood cells • Blood-forming cells first found in the yolk sac (primarily primitive rbc production) • HSCs arise in distal aorta ~3-4 weeks • HSCs migrate to the liver (primary site of hematopoiesis after 6 wks gestation) • Bone marrow hematopoiesis starts ~5 months of gestation Role of bone
    [Show full text]
  • Glossary of Medical Terms
    Glossary of Medical Terms A Absolute Neutrophil Count (ANC): The real number of white blood cells (WBCs) that are neutrophils. Neutrophils are key components in the system of defense against infection. Having few neutrophils present is called neutropenia. Acyclovir: An anti-viral drug used to treat or prevent cytomegalovirus and herpes simplex infections. Adenovirus: A set of viruses that induce respiratory tract and eye infections. Gene therapy uses adenoviruses that are modified to carry a particular tumor-fighting gene. Adrenal glands: Glands located on top of each kidney that secretes several important hormones into the blood. The inner portion of the adrenal gland, the adrenal medulla, stores and releases catecholamines that are measured by testing urine samples. Alkylating Agents: A class of anticancer drugs that interferes with the cell's DNA and restrains or halts cancer cell growth. Allogeneic: (Bone Marrow or Peripheral Blood Stem Cell Transplant) a transplant using bone marrow or stem cells from a matched sibling donor infused into recipient after high dose chemotherapy. Angiogenesis: Blood vessel formation. Angiogenesis involves the growth of blood vessels from surrounding tissue into a solid tumor. Antiangiogenesis drugs are drugs that prevent the growth of new blood vessels into a solid tumor. Anthracyclines: A class of antibiotics used in many induction chemotherapy regimens for high-risk neuroblastoma. It is important to keep track of the cumulative dose of anthracyclines a child receives because these drugs can damage the heart muscle. Antibiotics: Drugs used to fight bacterial infections. Antibody: A substance made by the immune system, used to defend the body against bacteria, viruses, toxins or tumors.
    [Show full text]
  • Two Branches of Immune System
    Two branches of immune system Innate Adaptive Characteristics of innate immunity –Act the same way in all individuals –Requires no previous exposure to pathogen –Seen in many types of animals –Available early in infection –Necessary for induction of adaptive immunity Characteristics of adaptive immunity – Specific to a given pathogen – Occurs within lifetime of the individual – Only in vertebrates – Takes time to mount specific response later in infection (4-5 days) Innate defenses • Barriers • Phagocytosis and inflammation • Complement • Natural killer cells Barriers • Mechanical/Physical • Chemical • Microbiological Phagocytosis Neutrophil Macrophage Inflammation Complement activation Adaptive Innate Fig. 2.18 Adaptive responses • Antibody production (B cells) • Cell mediated response (T cells) – Cytotoxic T cells= kill infected cells – Helper T cells= increase activity of other cells of the immune system (Macrophages, B cells) • Potentiate the function of accessory cells: – NK cells – Macrophages/neutrophils – Eosinophils – Basophils – Mast cells Adaptive responses are specific to antigen • Antigen= – Recognized as foreign= “non-self” – Generally protein – Can be carbohydrate or nucleic acid – Only portion of a protein recognized by receptor= epitope – Recognized by Ig of B cells or TCR of T cells Immunoglobulin= Antibody T cell receptor (TCR): recognizes Ag bound in cleft of MHC Questions • Where do cells of the immune system come from? • How is diversity in Ag receptors (Ig or TCR) accomplished? • How are lymphocytes activated in
    [Show full text]
  • Bone Marrow Biopsy
    BONE MARROW BIOPSY Appointment Date: ____________________________ Time______________________ LOCATION: Aultman Main Hospital: 2600 6th St. SW, Canton DEPARTMENT: Aultman Endoscopy/Minor Surgery Department on Main 2 SUMMARY OF THE EXAM: A bone marrow biopsy is a procedure done to remove a small amount of marrow from your bone. Bone marrow is the soft, spongy tissue inside of your larger bones that makes blood cells. The procedure lasts approximately 15 minutes. INSTRUCTIONS One week before your procedure Check with your doctor for specific instructions if you are taking aspirin, anti- inflammatory drugs, insulin, or anticoagulants (blood thinners) Make sure you have arrangements to have someone with you who can drive you home after your procedure. The evening before your procedure Do not eat or drink ANYTHING after midnight, unless otherwise instructed by your doctor. The day of your procedure Bring a complete list of all your medications including prescription and over-the counter medications, herbal supplements, and vitamins. Wear loose fitting clothes that will be comfortable for you to wear home. Leave valuables such as cash, credit cards or jewelry at home. Report to the Endoscopy/Minor Surgery Department at least one hour before your scheduled procedure time. You will be asked to sign a consent form to allow the doctor to perform the procedure. You will be escorted to the prep/recovery area, where you will change into a gown. Lockers are provided. Your family member/friend may wait for you in the waiting room. The nurse will start an intravenous (IV) line to provide fluids and sedation During your procedure You will lie on your side on a cart with your knees pulled up to your stomach Medicine will be given through your IV line to relax you and keep you comfortable.
    [Show full text]
  • Understanding the Immune System and Lymphoma
    Understanding the Immune System and Lymphoma The body’s immune system is comprised of a network of cells, tissues, and organs. This network operates together to eliminate harmful pathogens, like bacteria and viruses, as well as cancer cells from the body. The immune system provides two different types of immunity: • Innate (meaning “inborn” or “natural”) immunity — This type of immunity is provided by natural barriers in the body, substances in the blood, and specific cells that attack and kill foreign cells. Examples of natural barriers include skin,mucous membranes, stomach acid, and the cough reflex. These barriers keep germs (bacteria or viruses) and other harmful substances from entering the body. Inflammation (redness and swelling) is also a type of innate immunity. Blood cells that are part of the innate immune system include neutrophils, macrophages, eosinophils, and basophils. • Adaptive (meaning adapting to external forces or threats) immunity — This type of immunity is provided by the thymus gland, spleen, tonsils, bone marrow, circulatory system, and lymphatic system. B cells and T cells, the two main types of lymphocytes, carry out the adaptive immune response by recognizing and either inactivating or killing specific invading organisms. The adaptive immune system can then “remember” the identity of the invader, so that the next time the body is infected by the same invader, the immune response will develop more quickly and strongly. All normal cells have a limited lifespan. A self-destruct mechanism called apoptosis is triggered when cells become senescent (too old) or get damaged; this natural process is called apoptosis or programmed sequence of events that lead to the cell’s death.
    [Show full text]
  • The Bone Marrow As Sanctuary for Plasma Cells and Memory T-Cells: Implications for Adaptive Immunity and Vaccinology
    cells Review The Bone Marrow as Sanctuary for Plasma Cells and Memory T-Cells: Implications for Adaptive Immunity and Vaccinology Stefan A. Slamanig 1,2,† and Martijn A. Nolte 1,2,* 1 Department of Molecular Hematology, Sanquin Research, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands; [email protected] 2 Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands * Correspondence: [email protected] † Current address: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Abstract: The bone marrow (BM) is key to protective immunological memory because it harbors a major fraction of the body’s plasma cells, memory CD4+ and memory CD8+ T-cells. Despite its paramount significance for the human immune system, many aspects of how the BM enables decade-long immunity against pathogens are still poorly understood. In this review, we discuss the relationship between BM survival niches and long-lasting humoral immunity, how intrinsic and extrinsic factors define memory cell longevity and show that the BM is also capable of adopting many responsibilities of a secondary lymphoid organ. Additionally, with more and more data on the differentiation and maintenance of memory T-cells and plasma cells upon vaccination in humans being reported, we discuss what factors determine the establishment of long-lasting immunological memory in the BM and what we can learn for vaccination technologies and antigen design. Finally, using these insights, we touch on how this holistic understanding of the BM is necessary for the development of modern and efficient vaccines against the pandemic SARS-CoV-2. Citation: Slamanig, S.A.; Nolte, M.A.
    [Show full text]